Organoactinide-, organolanthanide-, and organogroup-4-mediated hydrothiolation of terminal alkynes with aliphatic, aromatic and benzylic thiols

ABSTRACT

An efficient and highly Markovnikov selective organoactinide-, organolanthanide-, and organozirconium-catalyzed addition of aryl, benzyl, and aliphatic thiols to terminal alkynes is described. The corresponding vinyl sulfides are produced with little or no side-products.

This application is a divisional of and claims priority to U.S.application Ser. No. 12/856,154 filed Aug. 13, 2010, which claimedpriority to U.S. provisional application Ser. 61/233,541 filed Aug. 13,2009-each of which is incorporated herein by reference in its entirety.

This invention was made with government support under Grant No.CHE0809589 awarded by the National Science Foundation. The governmenthas certain rights in the invention.

FIELD OF THE INVENTION

The present invention relates generally to atom-efficientorganoactinide-, organolanthanide-, and organoGroup-4-catalyzedintermolecular hydrothiolation of terminal alkynes or allenes. Themethods of the invention can be used to incorporate sulfur into organicframeworks, to synthesize carbon-carbon bond forming reagents, and tosynthesize vinyl cross-coupling reagents.

BACKGROUND OF THE INVENTION

Sulfur is a constituent of many important polymeric materials, naturalproducts, and synthetic reagents, providing impetus to devise efficientcatalytic methodologies for sulfur-carbon bond formation. The additionof S—H bonds across alkynes is an atom-economical route to a variety ofvinyl sulfides that can be achieved by several pathways, includingradical (Capella, L. et al., J. Org. Chem. 1996, 61, 6783-6789; Benati,L. et al., J. Chem. Soc., Perkin Trans. 1995, 1035-1038; Benati, L. etal., J. Chem. Soc., Perkin Trans. 1991, 2103-2109; Ichinose, Y. et al.,Chem. Lett. 1987, 16, 1647-1650; Griesbaum, K., Angew. Chem. Int. Ed.Engl. 1970, 9, 273-287) and catalytic processes (Sabarre, A.; Love, J.,Org. Lett. 2008, 10, 3941-3944; Corma, A. et al., Appl. Catal., A 2010,375, 49-54; Ananikov, Valentine P. et al., Chem. Eur. 12010, 16,2063-2071; Shoai, S. et al., Organometallics 2007, 26, 5778-5781;Kondoh, A. et al., Org. Lett. 2007, 9, 1383-1385; Fraser, L. R. et al.,Organometallics 2007, 26, 5602-5611; Delp, S. A. et al., Inorg. Chem.2007, 46, 2365-2367; Beletskaya, I. P. et al., Pure Appl. Chem. 2007,79, 1041-1056; Beletskaya, I. P. et al., Eur. J Org. Chem. 2007,3431-3444; Ananikov, V. P. et al., J. Am. Chem. Soc. 2007, 129,7252-7253; Malyshev, D. A. et al., Organometallics 2006, 25, 4462-4470;Ananikov, V. P. et al., Russ. Chem. Bull. 2006, 55, 2109-2113; Ananikov,V. P. et al., Organometallics 2006, 25, 1970-1977; Cao, C. et al., J.Am. Chem. Soc. 2005, 127, 17614-17615; Ananikov, V. P. et al., Adv.Synth. Catal. 2005, 347, 1993-2001; Kondo, T. et al., Chem. Rev. 2000,100, 3205-3220). Radical hydrothiolation yields unselective mixtures ofE and Z vinyl sulfides, while organometallic catalysts offer access toMarkovnikov vinyl sulfides or E anti-Markovnikov vinyl sulfides withvarying degrees of turnover and selectivity (Misumi, Y. et al., J.Organomet. Chem. 2006, 691, 3157-3164). While diverse variants oforganometallic complex-mediated hydroelementation have been extensivelyexplored, including hydroamination, hydrophosphination andhydroalkoxylation, only recently has hydrothiolation been investigatedin detail due to the historic reputation of sulfur as a catalyst poison(Hegedus, L. L.; McCabe, R. W., Chemical Industries Series, Vol. 17:Catalyst Poisoning. 1984), reflecting its high affinity for “soft”transition metal centers (Stephan, D. W. et al., Coord. Chem. Rev. 1996,147, 147-208; Krebs, B. et al., Angew. Chem. Int. Ed. Engl. 1991, 30,769-788).

Interest in homogeneous, catalytic alkyne hydrothiolation over the pastfew years has yielded a number of metal complexes competent to effectthis transformation using late transition metal catalysts (Field, L. D.et al., Dalton Trans. 2009, 3599-3614; Ogawa, A. et al., J. Am. Chem.Soc. 1999, 121, 5108-5114; Kuniyasu, H. et al., J. Am. Chem. Soc. 1992,114, 5902-5903). For example, Rh, Ir, Ni, Pd, Pt and Au complexes havebeen previously reported. While some late transition metal catalystsexhibit high activity, achieving high Markovnikov selectivity stillpresents a challenge, with the exception of Pd, as does competingisomerization of the alkene product, double-thiolation products andproduct insertion into a second alkyne. Furthermore, while some latetransition metal complexes effect efficient alkyne hydrothiolation withbenzyl and aryl thiols, few mediate hydrothiolation with the lessreactive aliphatic thiols. Previous work with rhodium catalystsdemonstrates the ability to utilize both terminal and internal alkyneswith selectivity typically favoring the linear E anti-Markovnikovproducts with the exception of Tp*Rh(PPh₃)₂, where Markovnikov vinylsulfides are selectively produced. Studies on group 10 metals find thatnickel and palladium catalysts favor the Markovnikov product.

Available mechanistic data for late transition metal-mediatedhydrothiolation complexes are consistent with pathways in which thealkyne undergoes insertion into either a metal-hydride or metal-thiolatebond. The accepted hydride pathway for most Rh complexes is initiated byπ-coordination/activation of the acetylene to/by the metal-hydridecomplex, followed by alkyne insertion into the Rh—H bond. Finally,regeneration of the catalyst occurs through reductive elimination ofproduct followed by RS—H oxidative addition to the metal center. Rhodiumcomplexes selectively yield E anti-Markovnikov products as a result ofthe hydride insertion regiochemistry. In contrast, Pd complexes areproposed to effect hydrothiolation via acetylene insertion into themetal-thiolate bond followed by thiol-mediated displacement of productfrom the metal center, resulting in Markovnikov selectivity.

The efficacy of inexpensive organozirconium complexes for formallyanalogous hydroamination processes has been reported (Leitch, D. C. etal., J. Am. Chem. Soc. 2009, 131, 18246-18247; Smolensky, E. et al.,Organometallics 2007, 26, 4510-4527; Ackermann, L. et al., J. Am. Chem.Soc. 2003, 125, 11956-11963; Arredondo, V. M. et al., Organometallics1999, 18, 1949-1960; Majumder, S. et al., Organometallics 2008, 27,1174-1177; Stubbert, B. D. et al., J. Am. Chem. Soc. 2007, 129,6149-6167). Likewise, lanthanide complexes have also been used inhydroamination (Andrea, T. et al., Chem. Soc. Rev. 2008, 37, 550-567;Müller, T. E. et al., Chem. Rev. 2008, 108, 3795-3892; Hartwig, J. F.,Nature 2008, 455, 314-322; Motta, A. et al., Organometallics 2006, 25,5533-5539; Alonso, F. et al., Chem. Rev. 2004, 104, 3079-3160; Motta, A.et al., Organometallics 2004, 23, 4097-4104; Hong, S. et al., Acc. Chem.Res. 2004, 37, 673-686; Ackermann, L. et al., J. Am. Chem. Soc. 2003,125, 11956-11963; Arredondo, V. M. et al., Organometallics 1999, 18,1949-1960; Arredondo, V. M. et al., J. Am. Chem. Soc. 1999, 121,3633-3639; Arredondo, V. M. et al., J. Am. Chem. Soc. 1998, 120,4871-4872; Haskel, A. et al., Organometallics 1996, 15, 3773-3775;Giardello, M. A. et al., J. Am. Chem. Soc. 1994, 116, 10241-10254;Gagne, M. R. et al., J. Am. Chem. Soc. 1992, 114, 275-294),hydrophosphination (Perrier, A. et al., Chem. Eur. 12009, 16, 64-67;Douglass, M. R. et al., J. Am. Chem. Soc. 2000, 122, 1824-1825;Douglass, M. R. et al., J. Am. Chem. Soc. 2001, 123, 10221-10238;Kawaoka, A. M. et al., Organometallics 2003, 22, 4630-4632; Motta, A. etal., Organometallics 2005, 24, 4995-5003; Nagata, S. et al., TetrahedronLett. 2007, 48, 6637-6640; Sadow, A. D. et al., J. Am. Chem. Soc. 2004,126, 14704-14705; Takaki, K. et al., J. Org. Chem. 2003, 68, 6554-6565;Wicht, D. K. et al., J. Am. Chem. Soc. 1997, 119, 5039-5040), andhydroalkoxylation processes (Motta, A. et al., Organometallics 2010, 29,2004-2012;. Dzudza, A. et al., Chem.-Eur. 12010, 16, 3403-3422; Seo, S.et al., Chem.-Eur. 12010, 16, 5148-5162; Cui, D.-M. et al., Synlett2009, 7, 1103-1106; Dzudza, A. et al., Org. Lett. 2009, 11, 1523-1526;Janini, T. E. et al., Dalton Trans. 2009, 10601-10608; Nishina, N. etal., Tetrahedron 2009, 65, 1799-1808; Seo, S. et al., J. Am. Chem. Soc.2009, 131, 263-276; Zhang, Z. et al., Org. Lett. 2008, 10, 2079-2081;Nishina, N. et al., Tetrahedron Lett. 2008, 49, 4908-4911; Harkat, H. etal., Tetrahedron Lett. 2007, 48, 1439-1442; Yu, X. et al., J. Am. Chem.Soc. 2007, 129, 7244-7245; Zhang, Z. et al., J. Am. Chem. Soc. 2006,128, 9066-9073; Yang, C. G. et al., Org. Lett. 2005, 7, 4553-4556; Qian,H. et al., J. Am. Chem. Soc. 2004, 126, 9536-9537). However, the use ofthese complexes in the hydrothiolation of alkynes has yet to bereported.

Accordingly, an efficient catalytic system is desired for thehydrothiolation of terminal alkynes by aromatic, benzylic, and lessreactive aliphatic thiols. This system should proceed with a high degreeof Markovnikov selectivity and reduce 1) the formation ofdouble-thiolated side product, 2) the competing isomerization of thealkene product, and 3) the product insertion into a second alkyne.

SUMMARY OF THE INVENTION

In light of the foregoing, it is an object of the present invention toprovide an organolanthanide, organoactinide, or organoGroup-4 catalystfor the intermolecular hydrothiolation of terminal alkynes using avariety of aryl, benzyl and aliphatic thiols, thereby overcoming variousdeficiencies and shortcomings of the prior art, including those outlinedabove. It will be understood by those skilled in the art that one ormore aspects of this invention can meet certain objectives, while one ormore other aspects can meet certain other objectives. Each objective maynot apply equally, in all its respects, to every aspect of thisinvention. As such, the following objects can be viewed in thealternative with respect to any one aspect of this invention.

It can also be an object of the present invention to provide anefficient method for a catalyzed addition of aryl, benzyl and aliphaticthiols to terminal alkynes to yield vinyl sulfides. In an aspect of theinvention, the method is Markovnikov-selective, and the vinyl sulfidesproduced by the method can also be free, or substantially free, of adouble-thiolated side product. Thus, the method comprises treating athiol with a terminal alkyne in the presence of a catalyst selected fromthe group consisting of an organolanthanide, organoactinide andorganoGroup-4 catalyst to afford a vinyl sulfide.

It is another object of the present invention to provide a vinyl sulfideprepared by treating a thiol with a terminal alkyne in the presence of acatalyst selected from the group consisting of an organolanthanide,organoactinide and organoGroup-4 catalyst.

Other objects, features, benefits and advantages of this invention wouldbe apparent from the summary, in conjunction with the followingdescriptions of certain embodiments, and will be readily apparent tothose skilled in the art. Such objects, features, benefits andadvantages will be apparent from the above as to taken into conjunctionwith the accompanying examples, data, figures and all reasonableinferences to be drawn therefrom, alone or with consideration of thereferences incorporated herein.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a representative plot of product formation rate against timefor CGCZrMe₂ (Zr-i)-mediated hydrothiolation 1A+2B→3AB. (A) Plot ofproduct formation rate of 1A+2A→3AA versus Zr-i; (B), [2A] and (C) [1A]at (D) [1A] and [2A]=0.2 M.

FIG. 2 is a plot of product formation rate for the reaction 1A+2B→3AB asa function of [Cp*₂SmCH(TMS)₂ (Ln-ix)] (A) and [2B] (B) with [1A] and[2B]=0.2 M; (C) plot of hydrothiolation conversion (%) versus time with17× molar excess 2A over 1A exhibits a linear trend indicating apseudo-zero-order reaction, demonstrating rate independence with respectto [1A] except at the highest concentrations where catalystprecipitation becomes extensive.

DETAILED DESCRIPTION OF THE INVENTION

In part, the present invention can be directed to a method of preparinga vinyl sulfide comprising treating a thiol with a terminal alkyne inthe presence of a catalyst selected from the group consisting of CGCM¹R¹₂, wherein M¹ is selected from an actinide metal and a Group 4 metal,and R¹ is selected from NMe₂, NEt₂ and Me; CGCM²R², wherein M² islanthanide metal and R² is N(TMS)₂; Cp*₂ M¹R³ ₂, wherein R³ is selectedfrom NMe₂, NEt₂, Me and CH₂TMS; Cp*₂M²R⁴, wherein R⁴ is selected fromN(TMS)₂ and CH(TMS)₂; Me₂SiCp″₂M³R⁵ ₂, wherein M³ is an actinide metal,and R⁵ is selected from CH₂TMS and Bn; M²[R⁴]₃; Cp*M⁴R⁶, wherein M⁴ is aGroup 4 metal and R⁶ is selected from Bn₃ and Cl₂NMe₂; and M³(R³)₄. Inan aspect of the invention, the thiol is selected from aryl, benzyl andaliphatic thiols.

The present invention can also be directed to a method of preparing avinyl sulfide comprising treating a thiol of the formula I

R″—SH  I

with an alkyne of formula II

≡—R′  II

to afford a corresponding vinyl sulfide of formula III

in the presence of a catalyst selected from the group consisting ofCGCM¹R¹ ₂, wherein M¹ is selected from an actinide metal and a Group IVmetal, and R¹ is selected from NMe₂, NEt₂ and Me; CGCM²R², wherein M² islanthanide metal and R² is N(TMS)₂; Cp*₂ M¹R³ ₂, wherein R³ is selectedfrom NMe₂, NEt₂, Me and CH₂TMS; Me₂SiCp″₂M³R⁵ ₂, wherein M³ is anactinide metal, and R⁵ is selected from CH₂TMS and Bn; M²[R^(4]) ₃;Cp*M⁴R⁶, wherein M⁴ is a Group 4 metal and R⁶ is selected from Bn₃ andCl₂NMe₂; and M³(R³)₄; and wherein R′ and R″ are independently selectedfrom the group consisting of alkyl, aryl, heteroaryl, cycloalkyl,arylalkyl, heteroarylalkyl and cycloalkylalkyl.

The general scheme for the hydrothiolation reaction of the invention isdepicted in Scheme 1.

By “alkyl” in the present invention is meant a straight or branchedchain alkyl radical having 1-20, and preferably from 1-12, carbon atoms.Examples include but are not limited to methyl, ethyl, propyl,isopropyl, n-butyl, sec-butyl, tert-butyl, pentyl, 2-pentyl, isopentyl,neopentyl, hexyl, 2-hexyl, 3-hexyl, and 3-methylpentyl. Each alkyl groupmay be optionally substituted with one, two or three substituents suchas, for example, a halo, cycloalkyl, aryl, alkenyl, hydroxy or alkoxygroup and the like.

By “aromatic” is meant an “aryl” or “heteroaryl” group.

By “aryl” is meant an aromatic carbocylic radical having a single ring(e.g. phenyl), multiple rings (e.g. biphenyl) or multiple fused rings inwhich at least one is aromatic (e.g. 1,2,3,4-tetrahydronaphthyl). Thearyl group can also be optionally mono-, di-, or trisubstituted with,for example, halo, alkyl, alkenyl, cycloalkyl, hydroxy or alkoxy and thelike.

By “heteroaryl” is meant one or multiple fused aromatic ring systems of5-, 6- or 7-membered rings containing at least one and up to fourheteroatoms selected from nitrogen, oxygen or sulfur. Examples includebut are not limited to furanyl, thienyl, pyridinyl, pyrimidinyl,benzimidazolyl and benzoxazolyl. The heteroaryl group can also beoptionally mono-, di-, or trisubstituted with, for example, halo, alkyl,alkenyl, cycloalkyl, hydroxy or alkoxy and the like.

By “cycloalkyl” is meant a carbocylic radical having a single ring (e.g.cyclohexyl), multiple rings (e.g. bicyclohexyl) or multiple fused rings(e.g. naphthlene). The cycloalkyl group can optionally contain from 1 to4 heteroatoms. In addition, the cycloalkyl group may have one or moredouble bonds. The cycloalkyl group can also be optionally mono-, di-, ortrisubstituted with, for example, halo, alkyl, alkenyl, aryl, hydroxy oralkoxy and the like.

By “alkoxy” is meant an oxy-containing radical having an alkyl portion.Examples include, but are not limited to, methoxy, ethoxy, propoxy,butoxy and tert-butoxy. The alkoxy group can also be optionally mono-,di-, or trisubstituted with, for example, halo, aryl, cycloalkyl orhydroxy and the like.

By “alkenyl” is meant a straight or branched hydrocarbon radical havingfrom 2 to 20, and preferably from 2-6, carbon atoms and from one tothree double bonds and includes, for example, ethenyl, propenyl,1-but-3-enyl, 1-pent-3-enyl, 1-hex-5-enyl. The alkenyl group can also beoptionally mono-, di-, or trisubstituted with, for example, halo, aryl,cycloalkyl or alkoxy and the like.

By “alkynyl” is meant a straight or branched hydrocarbon radical havingfrom 2 to 20, and preferably from 3-12, carbon atoms and from one tothree double bonds and includes, for example, propenyl, 1-but-3-enyl,1-pent-3-enyl, 1-hex-5-enyl. The alkenyl group can also be optionallymono-, di-, or trisubstituted with, for example, halo, aryl, cycloalkylor alkoxy and the like.

“Halo” is a halogen radical of fluorine, chlorine, bromine or iodine.

By “Group 4 metal” is meant Ti(IV), Zr(IV) and Hf(IV).

The following abbreviations/structures can be used interchangeablyherein:

CGC—Me₂SiCp″NCMe₃

Me—Methyl

Et—Ethyl

Bn—Benzyl

TMS—Trimethylsilyl

The present invention can also be directed to a vinyl sulfide of formulaIII

prepared by the steps comprising the step of reacting a thiol of formulaI

R″—SH  I

with a terminal alkyne of formula II

≡—R′  II

wherein R′ and R″ are independently selected from the group consistingof alkyl, aryl, heteroaryl, cycloalkyl, arylalkyl, heteroarylalkyl andcycloalkylalkyl, in the presence of a catalyst selected from the groupconsisting of CGCM¹R¹ ₂, wherein M¹ is selected from an actinide metaland a Group 4 metal, and R¹ is selected from NMe₂, NEt₂ and Me; CGCM²R²,wherein M² is lanthanide metal and R² is N(TMS)₂; Cp*₂ M¹R³ ₂, whereinR³ is selected from NMe₂, NEt₂, Me and CH₂TMS; Me₂SiCp″₂M³R⁵ ₂, whereinM³ is an actinide metal, and R⁵ is selected from CH₂TMS and Bn; M²[R⁴]₃;Cp*M⁴R⁶, wherein M⁴ is a Group 4 metal and R⁶ is selected from Bn₃ andCl₂NMe₂; and M³(R³)₄; and isolating the vinyl sulfide.

Preferably, R′ is C₁-C₆-alkyl, aryl, heteroaryl, C₃-C₇-cyloalkyl,aryl-C₁-C₆-alkyl, heteroaryl-C₁-C₆-alkyl or C₃-C₇-cyloalkyl-C₁-C₆-alkyl.Non-limiting examples of alkynes include 1-hexyne, ethynylcyclohexane,prop-2-ynylcyclohexane, 1-ethynylcyclohex-1-ene, 3-ethynylpyridine,prop-2-yn-1-amine or ethynylbenzene.

Preferably, R″ is C₁-C₁₂-alkyl, aryl, heteroaryl, C₃-C₇-cyloalkyl oraryl-C₁-C₆-alkyl. Non-limiting examples of thiols include1-pentanethiol, 1-pentanethiol-d, 1-dodecanethiol, cyclohexanethiol,2-methyl-2-butanethiol, benzyl mercaptan, 4-methylbenzyl mercaptan,prop-2-yn-1-amine or thiophenol.

Representative examples of suitable catalysts are those depicted inTable 1 below.

TABLE 1 Lanthanide Actinide Group 4

  Cp*₂SmN(TMS)₂ (Ln-i)

  Me₂SiCp″₂Th[CH₂(TMS)]₂ (An-i)

  CGCZrMe₂ (Zr-i)

  Cp*₂YN(TMS)₂ (Ln-ii)

  Me₂SiCp″₂UBn₂ (An-ii)

  Cp*₂ZrMe₂ (Zr-ii)

  CGCSmN(TMS)₂ (Ln-iii)

  CGCU(NMe₂)₂ (An-iii)

  Cp*ZrBn₃ (Zr-iii) La[N(TMS)₂]₃ (Ln-iv)

  CGCTh(NMe₂)₂ (An-iv) Zr[NMe₂]₄ (Zr-iv) Nd[N(TMS)₂]₃ U(NEt₂)₄Cp*ZrCl₂NMe₂ (Ln-v) (An-v) (Zr-v) Lu[CH(TMS)₂]₃ (Ln-vi)

  Cp*₂U(NMe₂)₂ (An-vi) Y[N(TMS)₂]₃ Cp*₂Th(CH₂TMS)₂ (Ln-vii) (An-vii)Cp*₂LaCH(TMS)₂ Cp*₂U(CH₂TMS)₂ (Ln-viii) (An-viii) Cp*₂SmCH(TMS)₂ (Ln-ix)Cp*₂LuCH(TMS)₂ (Ln-x) Cp*₂YCH(TMS)₂ (Ln-xi)

The present hydrothiolation process exhibits a high level of Markovnikovselectivity. This presumably reflects a four-membered transition state,with the alkyne insertion regiochemistry dictated by transition statesterics and bond polarity orientation Marks, T. J. et al., J. Am. Chem.Soc. 2009, 131, 2062-2063, incorporated in its entirety herein byreference. Additional competing, non-catalytic, anti-Markovnikovproducts are occasionally detected under the present reactionconditions. These products are, for the most part, formed in negligiblequantities. Anti-Markovnikov side-products can be further suppressedwith the addition of a radical inhibitor, as, for example, γ-terpinene,into the reaction mixture. Despite formal similarities to the proposedinsertion/protonolysis mechanisms of several Pd and Ni catalysts(Malyshev, D. A. et al., Organometallics 2006, 25, 4462-4470),double-thiolated side-products are surprisingly not observed in theinstant invention.

Hydrothiolation rates appear to be dependent on the type of thiol used.Changing from primary to secondary aliphatic thiols results insignificant rate depression, suggesting steric impediments in theturnover-limiting alkyne insertion. As much as 50× rate reduction isobserved in transitioning from a primary to a secondary thiol (Table 2).Aromatic thiol functionality also influences hydrothiolation rates. Forexample, use of a benzyl mercaptan (1G) or thiophenol increases theturnover frequency (N_(t)) greatly. The enhanced reactivity of aryl- andbenzyl-thiols likely reflects electronic factors. However, forbenzenethiol, any electronic gain is offset by increased sterics whencompared to 1-pentanethiol. The 4-methylbenzyl mercaptan yields thelargest thiol substrate N_(t), likely reflecting a combination offavorable electronics and sterics.

Alkyne structure also affects the rate of hydrothiolation, howeversteric encumberance exhibits a less pronounced influence than electroniccharacteristics. Switching from an α-monosubstituted to anα-disubstituted alkyne results in a moderate decrease in rate (Table 2).Similar to the aforementioned trend with thiols, alkyne electroniccharacteristics also play a prominent role in influencinghydrothiolation rates, with conjugated alkynes exhibiting significantlyenhanced rates. In particular, introduction of unsaturation α to the CCbond results in a 5× rate increase versus the unconjugated alkyne, whilephenylacetylene (2B) increases the activity versus thecyclohexylacetylene (2D). Rate enhancement is also observed with a3-ethynylpyridine, although not as pronounced as that for phenylsubstitution.

TABLE 2 N_(t) Thiol Alkyne Product (h⁻¹,° C.)

  1A

  2A

  3AA  5(90) 0.7(120)

  1A-d 2A

  3AA —

  3A-dA

  1B 2A

  3BA 1(110)

  1C 2A

  3CA 14(90)  27(110)

  1D 2A

  3DA 4(110) 1A

  2B

  3AB 5(90) 1D 2B

  3DB   8(110) 0.2(120) 1A

  2C

  3AC 6(110) 1A

  2D

  3AD 4(110) 1C 2D

  3CD 16(90)

  1E 2A

  3EA 0.6(120)

  1F 2A

  3FA 0.6(120)

  1G 2A

  3GA 3(120) 1A

  2E

  3AE 0.3(120) 1A

  2F

  3AF 1.5(120) 1A

  2G

  3AG 1.2(120) 1A

  2H

  3AH 4.8(120) 4.7(120)

In spite of some variations in conversion, good to excellentselectivities are observed for all thiols examined with 1-hexyne. Mostof the hydrothiolation reactions proceed with >90% Markovnikovselectivity (Table 3). Likewise, selectivity remains high when varyingthe alkyne, sometimes requiring the presence of a radical inhibitor suchas γ-terpinene.

TABLE 3 Selectivity Conversion Thiol Alkyne Catalyst (%) (%) 1E 2ALn-ix >99   ≧95 1A 2A Ln-ix >99   55 1B 2A Ln-ix 90 11 1G 2A Ln-ix >99  92 1D 2A Ln-ix 91 48 1E 2A Zr-i 96 95 1A 2A Zr-i 94 95 1B 2A Zr-i 59 551G 2A Zr-i 95 95 1D 2A Zr-i 94 94 1A 2D Ln-ix 88 26 1A 2E Ln-ix 95 20 1A2F Ln-ix 72 55 1A 2C Ln-ix 77 (with γ- 56 terpinene) 1A 2B Ln-ix 95(with γ- 39 terpinene) 1A 2D Zr-i 92 92 1A 2E Zr-i 96 98 1A 2F Zr-i 91100 1A 2C Zr-i 97 (with γ- 100 terpinene) 1A 2B Zr-i 66 100 1A 2D An-vii94 32 1G 2A An-vii 90 43 1D 2B An-vii 83 (with γ- 61 terpinene) 1A 2HZr-i 75 1A 2H Zr-iii 98

Ancillary ligand selection has consequences for the stability oforganolanthanide-, organoactinide- and organozirconium-complexes inhydrothiolation catalysis. While the addition of excess thiol to Ln-iv,for example, results in immediate precipitation, Cp-based ligationdelays precipitation. The non-bonded repulsions of the Cp-based ligandslikely suppress the formation of insoluble, highly aggregated metalcomplexes. Also, metal ionic radius exerts an influence on catalystthiolytic stability, with the smaller ions exhibiting greater resistanceto precipitation.

Kinetic studies are performed to define the hydrothiolation reactionpathway and to better understand the influence of [catalyst], [thiol],and [alkyne] on the sequence of reaction events. Experiments areconducted on the CGCZrMe₂ (Zr-i)-mediated hydrothiolation of 1-hexyne(2A) by 1-pentanethiol (1A), and kinetic results are plotted in FIG. 1.The empirical rate law is derived by systematically varyingconcentration of Zr-1,1A, and 2A at 120° C. Experiments carried out byvarying [Zr-i] over the range 1.9-21 mM exhibit a clear, linear trendwhen plotted against the measured rate (FIG. 1B) indicating afirst-order dependence of rate on catalyst concentration. By varying[2A] over the range 0.10-1.5 M, a first-order trend is also observed inthe plot of [2A] versus product formation rate (FIG. 1C). The varying of1A concentration reveals a more complex trend, with an approximatefirst-order behavior for [1A]<0.3 M, followed by saturation in the rateat concentrations >0.3 M (FIG. 1D). As a result, the empirical rate lawfor the reaction 1A+2A→3AA is described by Equation 1a with [Zr-i] and[2A] both first-order, and [1A] x-order with x=1 for [1A]<0.3 M and x=0for [1A]>0.3 M. Additional catalyst- and alkyne-dependance studiesperformed under high [thiol] conditions (i.e. [thiol]=1.2 M) show that[alkyne] and [catalyst] remain first-order even at elevated [thiol].

Rate=k _(obs) [Zr-i] ^(1[)2A] ^(1[)1A] ^(X)  (Equation 1a)

To derive activation parameters, the rate of the conversion 1A+2A →3AAmediated by Zr-i is analyzed from 50 to 80° C., and the data are plottedwith respect to the Eyring equation. Variable temperature studies at 0.2M [alkyne] and [thiol] result in an Eyring plot yieldingΔH^(‡)=+18.1(1.2) kcal/mol and ΔS^(‡)=−20.9(2.5) e.u. Repeating thetemperature studies with [thiol]=1.2 M from 40 to 80° C. yields similarreactions parameters of ΔH^(‡)=+17.8(1.5) kcal/mol and ΔS^(‡)=−24.4(4.8)e.u.

To trace the fate of the D-CC≡R′ hydrogens in the present catalytictransformations, deuterium-labeling experiments are performed usingdeuterated phenylacetylene (2B-d). Upon addition of 1A and 2B-d to Zr-iat room temperature, a single methane (CH₄) resonance is immediatelyobserved in the ¹H NMR spectrum. The absence of CH₃-D suggests exclusiveactivation of the catalyst by thiol protonolysis despite known alkyneprotonolysis activity. To further rule out alkyne-mediated protonolysisas a kinetically signifigant route for the cleavage of Zr-alkyl bonds,relative rates of alkyne- and thiol-mediated protonolysis are examinedin the activation of Cp*₂ZrMe₂ (Zr-ii). By addition of either 2A or 1Ato Zr-ii, thiol protonolysis of the Zr—Me bonds is measured to be 150×more rapid than the analogous alkyne protonolysis.

An apparent ME of k_(H)/k_(D)=1.3(0.1) is measured for the reaction 1A+2B-d catalyzed by complex Zr-i, consistent with a secondary kineticisotope effect. At early reaction times, a single olefinic resonanceappears in the ¹H NMR at δ 5.13 ppm assigned to a product 3AB-d_(E) by1D NOESY NMR. In addition, ²H NMR shows a single product deuteriumresonance at δ 5.4 ppm. Upon further heating, additional productolefinic resonances appear in the ¹H NMR spectra at δ 5.41, 5.40, and5.14 ppm with a second olefinic resonance in the ²H NMR at δ 5.1 ppmindicating the formation of products 3AB, 3AB-d_(z), and possibly 3AB-d₂(Scheme 2). Interestingly, a deuterium resonance is also observedgrowing in at δ 1.07 ppm indicating deuteration of the thiol (i.e.,RSD).

To further examine the deuterium exchange from alkyne-d to thiol,phenylacetylene-d (2B-d), t-butylmercaptan, and Zr-i were dissolved inbenzene-d₆ and heated at 120° C. for 9 hours. Despite no evidence ofzirconium-mediated hydrothiolation, deuterium/proton exchange isobserved by 1H and ²H NMR spectroscopy, indicating that the exchange isindependent of the zirconium-mediated hydrothiolation pathway. A similarcombination of 2B-d and 1A without catalyst evidences no deuteriumexchange showing that zirconium is involved in the isotopic exchangeprocess.

Kinetic experiments are also conducted on the Ln-ix-mediatedhydrothiolation of 2A by 1A in benzene-d₆ at 120° C. The empirical ratelaw is derived by examining the turnover-frequency (N_(t)) whilesystematically varying [catalyst], [alkyne], and [thiol]. By examiningLn-ix from 0.4-8.6 mM, a linear trend is observed for concentrations of0.4-5.2 mM (FIG. 2A), indicating a first-order dependence on [catalyst]at lower concentrations, while a fall in activity is observed at higherconcentrations. Attempts to explore the reaction at even higher Ln-ixvalues, 9-17 mM, results in reduced activity and rapid catalystprecipitation from solution. An investigation of the effects ofincreasing [1-hexyne] from 0.1-3.5 M reveals a linear correlation withactivity over the [1-hexyne] range, 0.1-0.9 M (FIG. 2B), indicatinginitial first-order dependence on [alkyne]. On increasing the alkyneconcentration further, a slight reduction in activity is observed whichmay be the result of partial alkyne saturation of the metal centerand/or alkyne acting as a hydrothiolation inhibitor. Finally, thedependence of N_(t) on [1-penthanethiol] from 0.01-0.2 M at 1-hexyneconcentrations (i.e., 3.5 M) to force the reaction to pseudo zero-ordershows the reaction to be zero-order with respect to [thiol] (FIG. 2C).The fall in rate near the end of the reaction corresponds to the onsetof observable catalyst precipitation. Therefore, the empirical rate law,under standard catalytic conditions with minimal catalyst precipitation,is given by Equation 1b.

Rate=k _(obs) [Sm] ¹[Alkyne]¹[Thiol]⁰  (Equation 1b)

To trace the fate of D-CC≡R′ during Ln-ix- and An-1-mediatedhydrothiolation, deuterium-labeling studies are performed usingdeuterated 2B-d and 1A. Exclusive observation of H₂C(TMS)₂ in the ¹H and²H NMR evidences thiol-mediated protonolytic activation of the catalyst.By comparing the activity with that of non-deuterated phenylacetylene,apparent KIEs of k_(H)/k_(D)=1.40(0.1) and 1.35(0.1) are observed forcatalysts Ln-ix and An-i, respectively. This is consistent with asecondary kinetic isotope effect in a turnover-limiting insertionmechanism. At early reaction times, a single product isotopomer isprimarily observed. However, upon further heating, other knownisotopomer products are observed, along with substantial loss of thephenylacetylene deuterium label. The observation of 3AB-dE product earlyin the reaction is consistent with thiol-mediated protonolysis. As thereaction progresses, increasing quantities of other product isotopomersform, corresponding to redistribution of the alkyne ²H label. Based on¹H and ²H NMR spectroscopy, deuterium is observed to migrate from thealkyne terminus to the thiol functionality, as evidenced by a prominentRSD resonance in the 2H NMR. To determine if the migration is the resultof the catalytic cycle, t-butylmercaptan, phenylacetylene-d, and eithercomplex Ln-ix or An-i are heated in benzene-d₆ at 120° C. for 0.75hours. Proton NMR integration indicates that 15-30% of the deuteriummigrates from the alkyne during this time period despite the fact thatno measurable hydrothiolation product is observed. A control experimentwithout the addition of catalyst results in no detectable deuteriumscrambling. The observed ²H exchange between phenylacetylene-d andt-BuSH, prior to significant catalytic turnover, as well as negligible²H migration in the absence of catalyst, strongly supports a metalcomplex pathway independent of the hydrothiolation catalytic cycle. Theknown protonolytic reactivity of terminal alkynes, with lanthanide- andactinide-heteroelement bonds suggests a pathway such as shown in Scheme3.

Interestingly, the more rapid formation of the product isotopomers inlanthanide- and actinide-mediated hydrothiolation than inzirconium-mediated hydrothiolation is consistent with the more polarbonding and larger ionic radii of lanthanide and actinide complexes andlanthanide and actinide complexes exhibiting a lowerprotonolytic/deuterolytic barrier. Bond enthalpy estimates indicate thatthe protonolytic detachment of alkyne from organo-Th or Sm complexes isca. −24 kcal/mol and −22 kcal/mol, respectively (Equation 2).

R″SH+M−C≡CR′→M−SR″+H—C≡CR′  (Equation 2)

Due to the Markonikov selectivity and exothermicity of thiol-mediatedprotonolysis of metal-alkynyl bonds, the metal-alkynyl

metal-thiolate equilibrium should strongly favor the correspondingthiolates. In the Ln-ix- and An-1-mediated hydrothiolation ofphenylacetylene-d by 1A, the formation of primarily 3AB-d₂ furthersupports the insertion/thiol-mediated protonolysis mechanism (Scheme 4).The observation of small quantities of 3AB early in the reactiondemonstrates the rapid nature of deuterium/proton scrambling between thealkyne and thiol positions.

While alkyne deuterolysis of M-vinyl product from the lanthanide oractinide center could result in ²H delivery to the Z product position,it seems more likely to originate from thiol-mediated deuterolysis ofproducts bound to the metal center (Scheme 5), because of the RSDdetected in situ by ²H NMR, and REH (E=O and S) protonolysis pathways inanalogous organozirconium-mediated hydrothiolation andlanthanide-mediated hydroalkoyxlation processes.

The disclosures in this application of all articles and references,including patents, are incorporated herein by reference.

The invention is illustrated further by the following examples which arenot to be construed as limiting the invention in scope or spirit to thespecific procedures described herein. The starting materials and variousintermediates may be obtained from commercial sources, prepared fromcommercially available compounds, or prepared using well known syntheticmethods. Representative examples of methods for preparing intermediatesof the invention are set forth below. All thiols, alkynes and vinylsulfide products of the examples below are named by ChemBioDraw Ultra,version 12.0.

EXAMPLES Materials and Methods

Due to the air and moisture sensitivity of the organoactinide complexesin this study, all manipulations are carried out in oven-dried,Schlenk-type glassware interfaced to either a dual-manifold Schlenkline, high-vacuum line (10⁻⁶ Torr), or in a nitrogen-filled glove box(<2 ppm O₂). Argon (Airgas) is further purified by passing it throughcolumns of MnO and activated 4 A Davison molecular sieves immediatelybefore use. Toluene-d₈ and benzene-d₆ (all 99+atom % D) for NMRreactions and kinetic measurements are stored over Na/K alloy in vacuoand vacuum transferred immediately prior to use or are stored in anitrogen-filled glovebox until use. Diethylether for synthesis isdistilled from Na/benzophenone immediately prior to use. D₂O (99+ atom %D) is used as received. Tetraglyme is vacuumed-pumped to removevolatiles. Ethanethiol-d (98 atom % D) is prepared according toliterature methods (Marks et al., J. Am. Chem. Soc. 2009, 131,2062-2063). Thiols and alkynes are transferred from multiple beds ofactivated Davison 4 A molecular sieves as solutions in benzene-d₆ orneat, followed by degassing (10⁻⁶ Torr) via freeze-pump-thaw methods.Conjugated alkynes and thiols are stored at −10° C. until use. Allsubstrates are stored under argon until use, and phenylacetylene and1-ethynylcyclohexene are distilled just prior to use. The catalysts areprepared as reported in the literature (see Stubbert; B. D., Marks, T.J. J. Am. Chem. Soc. 2007, 129, 6149-6167; Stubbert, B. D.; Marks, T. J.J. Am. Chem. Soc. 2007, 129, 4253-4271; and Stubbert, B. D.; Stern, C.L.; Marks, T. J. Organometallics 2003, 22, 4836-4838, all of which areincorporated herein by reference). The methyltriphenylsilane ¹H NMRinternal integration standard for kinetics is sublimed under high-vacuumand stored in a glove box until use.

Physical and Analytical Measurements.

NMR spectra are recorded on Mercury 400 (400 MHz, ¹H; 100 MHz, ¹³C; 61MHz, ²H) and Avance III 500 (500 MHz, ¹H; 125 MHz, ¹³C) NMRspectrometers. Chemical shifts (δ) are referenced relative to internalsolvent or integration standard resonances and reported relative toMe₄Si. Spectra of air-sensitive reactions and materials are taken inairtight, Teflon-valved J. Young NMR tubes. Samples are heated insilicon oil baths with the temperature controlled by an Ika ETS-D4probe. GC data for selectivity measurements are collected on a HP6890GC-MS equipped with a HP5972 detector and an HP-5MS (5% phenyl methylsiloxane, 30m×250 μm×0.25 μm) capillary column while high-resolutionmass spectra are collected on an Agilent 6210 LC-TOP (ESI, APPI) andThermo Finnegan MAT900 (EI).

Typical NMR Scale Catalytic Reaction.

a) In a glove box, Zr-i (3.7 mg, 10 μmol) and methyltriphenylsilane (8.0mg, 29.5 μmol are dissolved in 0.6 ml of C₆D₆ and added to a J. YoungNMR tube. The tube is sealed, removed from the glove box, and attachedto a high-vacuum line where 0.2 ml of thiol and 0.2 ml of alkynesolutions (both 1.0 M in benzene-d₆; 0 2 mmol; 20-molar excess) aresyringed in under an argon flush. The reaction mixture is then sealed,shaken well, degassed by a single freeze-pump-thaw cycle, and placed ina pre-heated, temperature controlled oil bath covered with aluminumfoil.

b) In a glove box, Ln-ix (3.0 mg, 5.2 μmol) and methyltriphenylsilane(8.0 mg, 29.5 μmol) are dissolved in 0.6 ml benzene-d₆ and added to a J.Young NMR tube. The tube is sealed, removed from the glove box, andattached to a high-vacuum line where 0.2 ml of thiol and 0.2 ml ofalkyne solutions (both 1.0 M in benzene-d₆; 0.2 mmol; 38-molar excess)are syringed in under an argon flush. The reaction mixture is thensealed, shaken well, degassed by a single freeze-pump-thaw cycle, andplaced in a pre-heated, temperature controlled oil bath covered withaluminum foil.

Typical NMR Scale Kinetic Experiment. The same procedure as describedabove is followed except that the sample is periodically cooled to roomtemperature to collect ¹H NMR spectra. Turnover frequency (N_(t)) isdetermined by the method of initial rate where data points are collectedearly in the reaction before the substrates are appreciably consumed. Asa result, the reaction during this period of time is approximated aspseudo-zero-order with respect to the substrate concentrations,resulting in a linear trend. The resulting linear plots are fit by alinear-regression analysis using R²≧0.99 according to Equation 3, andN_(t) is calculated according to Equation 4 where [catalyst]_(o)=initialconcentration of catalyst and t=time in hours. Kinetic experiments inthis study are performed at 0.2 M [thiol] and [alkyne] unless otherwiseindicated. Linear corrections for slight variations in initial [thiol]and [alkyne] are applied as needed.

$\begin{matrix}{\lbrack{product}\rbrack = {mt}} & {{Equation}\mspace{14mu} 3} \\{{N_{t}\left( h^{- 1} \right)} = \frac{m}{\lbrack{catalyst}\rbrack_{0}}} & {{Equation}\mspace{14mu} 4}\end{matrix}$

Yield and Selectivity Measurements.

a) In the glovebox, Zr-iv (5.0 mg, 10 μmol is dissolved in 0.4 ml ofC₆D₆ and the resulting solution is transferred to a J. Young NMR tube.The tube is then sealed, removed from the glovebox, and attached to ahigh-vacuum line where 0.2 ml of thiol and 0.6 ml of alkyne solutions(both 1.0 M in benzene-d₆; 0.2 mmol; 20-molar excess in thiol) aresyringed in under an argon flush. The reaction mixture is then sealed,shaken, degassed by a single freeze-pump-thaw cycle, and placed in atemperature-controlled, 120° C. oil bath for 24.0 hours. The productconversion and selectivity are determined by ¹H NMR and GC/MS.

b) In a glove box, Ln-ix (5.0 mg, 10 μmol is dissolved in 0.4 mlbenzene-d₆ and the resulting solution transferred to a J. Young NMRtube. The tube is then sealed and attached to a high-vacuum line where0.2 ml thiol and 0.6 mL alkyne solutions (both 1.0 M in benzene-d₆; 0.2mmol; 20-molar excess in thiol) are syringed in under an argon flush.The reaction mixture is then sealed, shaken, and placed intemperature-controlled, 120° C. oil bath for 16.0 hours. The productselectivity is determined by GC/MS while conversion is determined by ¹HNMR integrations against internal standards or quantitatively liberatedcatalyst ligands.

General Procedure for Purification of Products.

The reaction mixture is cooled to room temperature and the contents areeluted through a silica gel plug with ˜10 ml of hexanes to remove thecatalyst. The filtrate is pumped with a Schlenk line to removevolatiles. Further purification by flash chromatography (ether:hexaneseluent) is performed when necessary. To avoid degradation, some productsare purified by precipitating the catalyst from exposure to air,centrifuging the precipitated catalyst, and decanting the solution.Volatiles are pumped off on a Schlenk line to yield pure product.

General Preparative Scale Procedure.

a) In a glovebox, Zr-iv (220 mg, 0.44 mmol) is added to an oven-dried,20 ml J. Young-valved glass storage tube with a stir bar and dissolvedin 10 ml of toluene. The tube is then sealed and placed on a high-vacuumline where 1A (1.0 ml, 8.1 mmol) and 2A (2.5 ml, 22 mmol) are syringedinto the tube under an argon flush. The vessel is next sealed and placedin a preheated 100° C. oil bath for 24 hours. After cooling, the vesselis opened to ambient and the catalyst is removed by filtering throughsilica gel, eluting with ˜20 ml of hexanes. The volatiles are thenremoved under vacuum to yield pure 3AA as a yellow oil (1.08 g, 5.8mmol, 72% yield) which is determined to be 99% Markovnikov pure byGC/MS.

b) In a glove box, Ln-ix (75 mg, 0.13 mmol) is added to an oven dried,20 ml Teflon-valved, glass storage tube dissolved in 1 ml benzene. On ahigh-vacuum line, an additional 9 ml of benzene are added by vacuumtransfer. The tube is cooled to −78° C. and 2A (7,0.90 ml, 7.8 mmol) and1F (0.30 ml, 2.6 mmol) are syringed into the tube under an argon flush.The vessel is sealed, thawed, and placed in a pre-heated 120° C. oilbath for 36.0 hours with no stirring. Under ambient conditions, thecatalyst is removed by filtering through silica gel and eluting with 20ml hexanes. The volatiles are then removed under vacuum (10⁻⁶ mTorr) toyield 97% Markovnikov-pure 3FA as a yellow oil (0.22 g, 1.1 mmol, 41%yield).

Example 1 a) pentane-1-thiol-d

An oven-dried, 200 ml Schlenk flask is charged with LiH (0.72 g, 91mmol) and a magnetic stir bar. While under nitrogen, 50 ml of drytetraglyme is cannulated into the flask and stirred vigorously to form aslurry. The flask is cooled to 0° C. before dropwise addition of dry 1A(8.4 g, 80.6 mmol). The reaction is allowed to warm to room temperatureand then stirred for 1 hour followed by recooling to 0° C. and dropwisequenching with D₂O (2.5 ml, 140 mmol). The product 1A-d isvacuum-transferred from the tetraglyme and dried over 4 A molecularsieves before use (˜2.5 g, 30% yield). ¹H NMR (benzene-d₆, 400 MHz, 6):δ 2.17 (q, J=7.2 Hz, 2H); 1.34 (m, 2H); 1.12 (m, 4H); 0.79 (t, J=5.6 Hz,3H). ²H NMR (benzene-d₆, 76.7 MHz, δ): δ 1.09 (s). ¹³C NMR (benzene-d₆,100 MHz, δ): δ 33.9; 30.8; 24.9; 22.3; 14.2.

b) Ethanethiol-d (1E-d)- ¹H NMR (benzene-d₆, 500 MHz, δ): δ 2.16 (m,2H); 0.97 (t, 7.0 Hz, 1H). ¹³C NMR (benzene-d₆, 125 MHz, δ): δ 20.1;19.3. 2H (benzene-d₆, 61 MHz, δ): δ 1.07 (s).

Example 2 a) phenylacetylene-d

In an oven-dried, 200 ml Schlenk flask, phenylacetylene (7.0 ml, 64mmol) is dissolved in 60 ml of anhydrous diethylether. The flask iscooled to 0° C. before the slow addition of 45 ml of n-BuLi solution(1.6 M in hexanes, 72 mmol) and stirring for 15 minutes at 0° C.,followed by 30 minutes at room temperature. The flask is recooled to 0°C., and D₂O (2.5 ml, 125 mmol) is slowly added. The reaction is stirredovernight at room temperature before the solvent is removed in vacuo,and the product is distilled to afford a clear liquid in 57% yield. Thedeuterium incorporation is determined to be 98% atom % D by

¹H NMR. ¹H NMR (benzene-d₆, 500 MHz, δ): δ 7.40 (m, 2H); 6.91 (m, 3H).¹³C NMR (benzene-d₆, 125 MHz, δ): δ 132.7; 129.1; 128.9; 123.1; 83.8 (t,7.5 Hz); 78.0 (t, 38 Hz). 2H (benzene-d₆, 61 MHz, δ): δ 2.68 (s).

Example 3 a) hex-1-en-2-yl(pentyl)sulfane

In a glove box, An-iv (140 mg, 0.25 mmol) is added to an oven-dried, J.Young-valved glass tube with stir bar. The tube is sealed, placed on ahigh-vacuum line where toluene (30 ml) is vacuum transferred from Na/Kto dissolve the catalyst. Under an argon flush, 1A (0.60 ml, 4.8 mmol)and 2A (0.65 m, 5.7 mmol) are syringed into the tube, degassed byfreeze-pump-thaw, sealed, and placed in a pre-heated 120° C. oil bathfor 24 hours. Next, the vessel is opened to ambient surroundings andcatalyst is removed by filtering through silica gel and eluting withhexanes. The product is purified by flash chromatography (SiO₂, elutedwith 5:1 hexanes/ethyl acetate) and pumped down on a Schlenk line toyield pure 3AA as a yellow oil (0.62 g, 3.3 mmol, 69% yield).

¹H NMR (benzene-d₆, 400 MHz, 6): δ 5.34 (s, 1H); 4.72 (s, 1H); 2.53 (t,J=7.2 Hz, 2H); 2.25 (t, J=8.0 Hz, 2H); 1.63-1.47 (m, 4H); 1.34-1.08 (m,6H); 0.90-0.75 (m, 6H). ¹³C NMR (benzene-d₆, 125 MHz, 6): δ 147.2;105.1; 38.2; 31.9; 31.8; 31.7; 28.6; 22.9; 22.8; 14.5; 14.4. HRMS-EI(m/z): M⁺ calcd for C₁₁H₂₂S, 186.144. found, 186.144.95% yield; 94%Markovnikov-selective.

Example 4

The following compounds are prepared using essentially the sameprocedure as that described in the schemes, with reaction temperature asthat found in Table 2, and the general and specific examples of above.

a) cyclohexyl (hex-1-en-2-yl)sulfane

(yellow oil) ¹H NMR (benzene-d₆, 500 MHz, 6): δ 5.07 (s, 1H); 4.85 (s,1H); 2.94 (m, 1H); 2.22 (t, J=7.5 Hz, 2H); 1.98 (m, 2H); 1.57 (m, 4H);1.38 (m, 3H); 1.27 (m, 2H); 1.11 (m, 3H); 0.85 (t, J=7.5 Hz, 3H). ¹³CNMR (benzene-d₆, 125 MHz, δ): δ 145.8; 107.4; 50.42; 43.4; 38.4; 33.5;31.7; 26.5; 22.8; 14.4. HRMS-EI (m/z): M⁺ calcd for C₁₂H₂₂S 198.144.found, 198.144. 55% yield; 59% Markovnikov-selective.

b) hex-1-en-2-yl(4-methylbenzyl)sulfane

(dark yellow oil) ¹H NMR (benzene-d₆, 400 MHz, δ): δ 7.20-7.14 (m, 2H);6.94-6.90 (m, 2H); 5.00 (s, 1H); 4.76 (s, 1H); 3.72 (s, 2H); 2.21 (m,3H); 2.06 (s, 3H); 1.53 (m, 2H); 1.22 (m, 2H); 0.81 (m, 3H). ¹³C NMR(benzene-d₆, 100 MHz, δ): δ 147.2; 137.1; 134.5; 129.8; 129.5; 106.2;38.0; 36.6; 31.7; 22.7; 21.3; 14.4. HRMS-EI (m/z): M⁺ calcd for C₁₄H₂₀S,220.129. found, 220.128.

c) pentyl(1-phenylvinyl)sulfane

(dark yellow oil) ¹H NMR (benzene-d₆, 500 MHz, 6): δ 7.63 (d, J=7.5 Hz,2H); 7.12 (dd, J=7.5 Hz, 2H); 7.07 (m, 1H); 5.41 (s, 1H); 5.14 (s, 1H);2.48 (t, J=7.5 Hz, 2H); 1.48 (t, J=7.5 Hz, 2H); 1.20-1.05 (m, 4H); 0.77(t, J=7.0 Hz, 3H). ¹³C NMR (benzene-d₆, 125 MHz, 6): δ 140.5; 129.0;128.9; 127.9; 110.7; 32.6; 28.9; 22.9; 21.6; 14.4. HRMS-EI (m/z): M⁺calcd for C₁₃H_(i8)S, 206.113. found, 206.113. 100% yield; 66%Markovnikov-selective.

d) (1-(cyclohex-1-en-1-yl)vinyl)(pentyl)sulfane

(dark yellow oil) ¹H NMR (benzene-d₆, 500 MHz, 6): δ 6.43 (s, 1H); 5.29(s, 1H); 4.97 (s, 1H); 2.54 (t, J=7.5, 2H); 2.23-2.18 (m, 2H); 1.99-1.94(m, 2H); 1.58-1.50 (m, 2H); 1.52-1.47 (m, 2H); 1.42-1.36 (m, 2H),1.27-1.19 (m, 2H); 1.20-1.12 (m, 2H); 0.80 (t, J=7.0, 3H). ¹³C NMR(benzene-d₆, 125 MHz, δ): δ 147.1; 136.4; 1277; 107.2; 32.5; 31.8; 29.0;27.7; 26.3; 23.5; 23.0; 22.8; 14.5. HRMS-EI (m/z): M⁺ calcd for C₁₃H₂₂S,210.144. found 210.143. 100% yield; 75% Markovnikov-selective.

e) (1-cyclohexylvinyl)(pentyl)sulfane

(yellow oil) ¹H NMR (benzene-d₆, 500 MHz, 6): δ 5.07 (s, 1H); 4.67 (s,1H); 2.53 (t, J=7.0 Hz, 2H); 2.14 (t, J=11.5 Hz, 1H); 1.98 (d, J=12.5Hz, 2H); 1.68 (d, J=12.5 Hz, 2H); 1.54 (t, 7.5, 3H); 1.40 (m, 2H);1.25-1.02 (m, 7H); 0.80 (t, J=7.0 Hz, 3H). ¹³C NMR (benzene-d₆, 125 MHz,δ): δ 153.1; 102.7; 47.1; 33.9; 31.9; 31.6; 28.5; 27.3; 26.8; 23.0;14.5. HRMS-EI (m/z): M⁺ calcd for C₁₃H₂₄S, 212.160. found, 212.159.92%yield; 92% Markovnikov-selective.

f) (1-cyclohexylvinyl) (4-methylbenzyl)sulfane

(dark yellow oil) ¹H NMR (benzene-d₆, 400 MHz, 6): δ 7.16 (d, J=8.0 Hz,2H); 6.92 (d, J=8.0 Hz, 2H); 5.05 (s, 1H); 4.71 (s, 1H); 3.73 (s, 2H);2.11 (m, 1H); 2.07 (s, 3H); 1.96 (m, 2H); 1.64 (m, 2H); 1.52 (m, 2H);1.37 (m, 2H); 1.11 (m, 3H). ¹³C NMR (benzene-d₆, 100 MHz, 6): δ 153.0;137.0; 134.5; 129.7; 129.5; 103.8; 46.9; 36.6; 33.8; 27.2; 26.8; 21.4.HRMS-EI (m/z): M⁺ calcd for C₁₆H₂₂S, 246.144. found, 246.144.

g) ethyl(hex-1-en-2-yl)sulfane

¹H NMR (benzene-d₆, 500 MHz, δ): δ 5.01 (s, 1H); 4.66 (s, 1H); 2.43 (q,7.5 Hz, 2H); 2.22 (t, 7.5 Hz, 2H); 1.55 (m, 2H); 1.24 (m, 2H); 1.06 (t,7.5 Hz, 3H); 0.83 (t, 7.5 Hz, 3H). ¹³C NMR (benzne-d₆, 125 MHz, δ): δ146.8; 105.2; 38.1; 31.8; 25.6; 22.7; 14.4; 13.7. HRMS (EI) m/z calcdfor C₈H₁₆S: 144.0973. found: 144.0966.95% yield; 96%Markovnikov-selective.

h) hex-1-en-2-yl(2,2,2-trifluoroethyl)sulfane

¹H NMR (benzene-d₆, 400 MHz, δ): δ 4.90 (s, 1H); 4.75 (s, ¹H); 2.69 (q,10 Hz, 2H); 2.00 (t, 7.6 Hz, 2H); 1.34 (m, 2H); 1.40-1.30 (m, 2H);1.17-1.07 (m, 2H); 0.78 (t, 7.2 Hz, 3H). ¹³C NMR (benzene-d₆, 100 MHz,δ): δ 143.5; 129.0; 110.2; 36.9; 33.8 (q, J_(FC)=10 Hz); 31.0; 22.5;14.3. HRMS (EI) m/z calcd for C₈H₁₃F₃S: 198.0690. found: 198.0684.79%yield; 84% Markovnikov-selective.

i) benzyl(hex-1-en-2-yl)sulfane

¹H NMR (benzene-d₆, 500 MHz, δ): δ 7.22 (d, 7.5 Hz, 2H); 7.08 (t, 8.0Hz, 2H); 7.01 (t, 7.5, 1H); 4.98 (s, 1H); 4.73 (s, 1H), 3.69 (s, 2H);2.19 (t, 7.5 Hz, 2H); 1.51 (m, 2H); 1.22 (m, 2H); 0.81 (t, 7.5, 3H).^(B)C NMR (benzene-d₆, 125 MHz, δ): δ 147.0; 137.6; 129.5; 129.0; 127.6;106.3; 37.9; 36.8; 31.7; 22.7; 14.4. HRMS (EI) m/z calcd for C₁₃H_(i8)S:206.1129. found: 206.1127.95% yield; 95% Markovnikov-selective.

j) (3-cyclohexylprop-1-en-2-yl) (pentyl)sulfane

¹H NMR (benzene-d₆, 500 MHz, δ): δ 5.02 (s, 1H); 4.74 (s, 1H); 2.53 (t,7.0 Hz, 2H); 2.18 (d, 7.0 Hz, 2H); 1.83-1.78 (m, 2H); 1.78-1.70 (m, 1H);1.70-1.63 (m, 2H); 1.63-1.56 (m, 1H); 1.56-1.48 (m, 2H); 1.26-1.04 (m,7H); 0.87-0.78 (m, 5H). ¹³C NMR (benzene-d₆, 125 MHz, 6): δ 145.5;106.0; 46.7; 37.3; 33.6; 31.9; 31.7; 28.6; 27.3; 27.0; 22.9; 14.5. HRMS(EI) m/z calcd for C₁₄H₂6_(S): 226.1755. found: 226.1748.98% yield; 96%Markovnikov-selective.

k) pentyl (3-phenylprop-1-en-2-yl)sulfane

¹H NMR (benzene-d₆, 500 MHz, δ): δ 7.20-7.16 (m, 2H); 7.15-7.10 (m, 2H);7.06-7.01 (m, 1H); 4.96 (s, 1H); 4.73 (s, 1H); 3.44 (s, 2H); 2.42 (t,7.5 Hz, 2H); 1.44-1.36 (m, 2H); 1.13-1.01 (m, 4H); 0.72 (t, 7.0 Hz, 3H).^(B)C NMR (benzene-d₆, 125 MHz, δ): δ 146.4; 139.5; 129.7; 128.9; 127.1;107.1; 44.5; 31.9; 31.8; 28.5; 22.9; 14.4. HRMS (EI) m/z calcd forC₁₄H₂₀S: 220.1286. found: 220.1287. 100% yield; 91%Markovnikov-selective.

1) 3-(1-(pentylthio)vinyl)pyridine

¹H NMR (benzene-d₆, 500 MHz, δ): δ 9.05 (s, 1H); 8.46 (dd, 5.0 Hz, 1H);7.59 (dt, 8.0 Hz, 1H); 6.66 (dd, 8.0 Hz, 1H); 5.24 (s, 1H); 5.04 (s,1H); 2.37 (t, 7.5 Hz, 2H); 1.40 (m, 2H); 1.15-1.05 (m, 4H); 0.77 (t, 7.0Hz, 3H). ¹³C NMR (benzene-d₆, 125 MHz, δ): δ 150.4; 149.2; 143.2; 136.1;134.5; 123.4; 112.0; 32.5; 31.5; 28.7; 22.8; 14.4. HRMS (APPI) m/z[M+H]⁺ calcd for C₁₂H₁₇NS: 208.1161. found: 208.1158. 100% yield; 90%Markovnikov-selective.

m) 2-(pentylthio)prop-2-en-1-amine

¹H NMR (benzene-d₆, 500 MHz, 6): δ 5.16 (s, 1H); 4.74 (s, 1H); 3.26 (s,2H); 2.49 (t, 7.5 Hz, 2H); 1.49 (m, 2H); 1.26-1.06 (m, 4H); 0.87-0.63(bm, 5H). ¹³C NMR (benzene-d₆, 125 MHz, 6): δ 149.5; 105.1; 48.8; 31.8;31.5; 28.8; 22.9; 14.5. HRMS (ESI) m/z [M+H]⁺ calcd for C₈H_(i8)NS:160.1154. found: 160.1155.

Table 4 shows representative examples of compounds made and the catalystand solvent employed. The reactions are performed at temperaturesranging from 90-120° C. While titanium is not specifically listed in thetable, the metal is employed in complexes for methods of the invention.As with other Group 4 metals, optimization may vary with reactionconditions.

TABLE 4 Thiol Alkyne Catalyst Solvent 1H 2B Ln-i Benzene-d₆(Dodecanethiol) 1H 2B Ln-i THF-d₈ 1H 2B Ln-ii Benzene-d₆ 1H 2A Ln-iBenzene-d₆ 1C 2B Ln-i Benzene-d₆ 1A 2A Ln-v THF-d₈ 1B 2A Ln-i Benzene-d₆1B 2A Ln-ix Benzene-d₆ 1A 2A Ln-iv THF-d₈ 1D 2A Ln-v THF-d₈ 1D 2A Ln-ixBenzene-d₆ 1A 2A Ln-ii Benzene-d₆ 1A 2A Ln-vi Benzene-d₆ 1A 2A Ln-ixBenzene-d₆ 1G 2A Ln-ix Benzene-d₆ 1A 2A Zr-ii Benzene-d₆ 1A 2A An-iiiBenzene-d₆ 1D 2B An-iv Benzene-d₆ 1D 2B An-ii Benzene-d₆ 1C 2B An-iiBenzene-d₆ 1A 2B An-iii Benzene-d₆ 1A 2A Zr-iii Benzene-d₆ 1A 2A Zr-iiBenzene-d₆ 1A 2A Zr-i Benzene-d₆ 1G 2A Zr-i Benzene-d₆ 1G 2A Zr-iiiBenzene-d₆ 1G 2A Zr-iv Benzene-d₆ 1G 2A Zr-v Benzene-d₆ 1D 2A Zr-iiiBenzene-d₆ 1A 2D Zr-i Benzene-d₆ 1A 2D An-vii Benzene-d₆ 1G 2A An-viiBenzene-d₆ 1D 2B An-vii Benzene-d₆ 1A 2C Zr-i Benzene-d₆ 1A 2B Zr-iBenzene-d₆ 1A 2G Zr-i Benzene-d₆ 1A 2E Zr-i Benzene-d₆ 1A 2H Zr-iiiBenzene-d₆ 1A 2H Zr-i Benzene-d₆ 1B 2A Zr-i Benzene-d₆ 1H 2A Zr-iBenzene-d₆ 1H 2A Zr-iii Benzene-d₆ 1A 2A Zr-iv Benzene-d₆ 1H 2A Zr-ivBenzene-d₆ 1E 2A Zr-i Benzene-d₆ 1E 2A Ln-ix Benzene-d₆ 1F 2A Zr-iBenzene-d₆ 1D 2A Zr-i Benzene-d₆ 1A 2F Zr-i Benzene-d₆

The catalytic organolanthanide-, organoactinide- andorganozirconium-mediated intermolecular hydrothiolathion of a wide rangeof terminal alkynes by aliphatic, benzylic and aromatic thiols isdemonstrated by the methods disclosed herein. The resulting vinylsulfides are produced with high Markovnikov selectivity. Based onkinetic experiments and deuterium labeling, the reaction is proposed toproceed through an alkyne insertion-thiol protonolysis sequence withturnover-limiting alkyne insertion.

The invention and the manner and process of making and using it are nowdescribed in such full, clear, concise and exact terms as to enable anyperson skilled in the art to which it pertains, to make and use thesame. It is to be understood that the foregoing describes preferredembodiments of the present invention and that modifications may be madetherein without departing from the spirit or scope of the presentinvention as set forth in the claims.

What is claimed is:
 1. A vinyl sulfide of formula

prepared by the steps comprising 1) reacting a thiol of formula R″—SH with a terminal alkyne of formula II ≡—′ in the presence of a catalyst selected from the group consisting of; a) CGCM¹R¹ ₂, wherein M¹ is selected from an actinide metal and Zr(IV), and R¹ is selected from NMe₂, NEt₂ and Me; b) CGCM²R², wherein M² is lanthanide metal and R² is N(TMS)₂; c) Cp*₂ M¹R³ ₂, wherein R³ is selected from NMe₂, NEt₂, Me and CH₂TMS; d) Cp*₂M²R⁴, wherein R⁴ is selected from N(TMS)₂ and CH(TMS)₂; e) Me₂SiCp″M³R⁵ ₂, wherein M³ is an actinide metal, and R⁵ is selected from CH₂TMS and Bn; M¹[R⁴]₃; g) Cp* M⁴R⁶, wherein M⁴ is a Group 4 metal and R⁶ is selected from Bn and Cl₂NMe₂; and M⁴(R³)₄; and h) M⁴(R³)₄, wherein R′ and R″ are independently selected from the group consisting of alkyl, aryl, heteroaryl, cycloalkyl, arylalkyl, heteroarylalkyl and cycloalkylalkyl; and 2) isolating the vinyl sulfide.
 2. A vinyl sulfide of claim 1 wherein the catalyst is selected from Cp^(*) ₂SmN(TMS)₂, Me₂SiCp″₂Th[CH₂(TMS)]₂. CGCZrMe₂, Cp^(*) ₂YCH(TMS)₂, Me₂SiCp″₂UBn₂, Cp^(*) ₂ZrMe₂, CGCSmN(TMS)₂, CGCU(NMe₂)₂, Cp*ZrBn₃, La[N(TMS)₂]₃, CGCTh(NMe₂)₂, Zr[NMe₂]₄, Nd[N(TMS)₂]₃, U(NEt₂)₄, Cp*ZrCl₂NMe₂, Lu[CH(TMS)₂]₃, Cp^(*) ₂U(NMe₂)₂, Y[N(TMS)₂]₃, Cp^(*) ₂Th(CH₂TMS)₂, Cp^(*) ₂LaCH(TMS)₂, Cp^(*) ₂U(CH₂TMS)₂, Cp^(*) ₂SmCH(TMS)₂, and Cp^(*) ₂LuCH(TMS)₂.
 3. A vinyl sulfide according to claim 1 selected from the group consisting of a) hex-1-en-2-yl(pentyl)sulfane; b) cyclohexyl(hex-1-en-2-yl)sulfane; c) hex-1-en-2-yl(4-methylbenzyl)sulfane; d) pentyl(1-phenylvinyl)sulfane; e) (1-(cyclohex-1-en-1-yl)vinyl)(pentyl)sulfane f) (1-cyclohexylvinyl)(pentyl)sulfane; g) (1-cyclohexylvinyl)(4-methylbenzyl)sulfane; h) ethyl(hex-1-en-2-yl)sulfane; i) hex- 1-en-2-yl(2,2,2-trifluoroethyl)sulfane; j) benzyl(hex-1-en-2-yl)sulfane; k) (3-cyclohexylprop-1-en-2-yl)(pentyl)sulfane; l) pentyl(3-phenylprop-1-en-2-yl)sulfane; m) 3-(1-(pentylthio)vinyl)pyridine; and n) 2-(pentylthio)prop-2-en-1-amine. 